Metaproteomics as a tool for studying the protein landscape of human-gut bacterial species.

Metaproteomics as a tool for studying the protein landscape of human-gut bacterial species.
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DOI:
10.1371/journal.pcbi.1009397
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发表时间:
2022-03
影响因子:
4.3
通讯作者:
Ye Y
Ye Y
中科院分区:
生物学2区
文献类型:
--
作者:
Stamboulian M;Canderan J;Ye Y

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宿主-微生物组相互作用和微生物群落对人类健康和疾病具有广泛的影响。大多数基于微生物组的研究都是基于下一代测序技术在基因组水平上进行的,但元蛋白质组学正在成为一种强大的技术,通过表征微生物蛋白质的复杂和动态组成来研究微生物组的功能活性。我们对人类肠道微生物组元蛋白质组数据进行了大规模调查,以确定在所有样品中普遍表达的通才物种和在与某种表型相关的一小部分样品中高度表达的专家。我们能够利用元蛋白质组质谱数据来揭示这些物种的蛋白质景观,这使得能够表征不同功能蛋白质的表达水平和潜在的调节机制(例如操纵子)。最后,我们能够恢复大量的开放阅读框架(ORF)的光谱支持,这是错过了从头蛋白质编码基因的预测。我们发现,大多数获救的ORF与从头预测的蛋白质编码基因重叠,但在相反的链或不同的框架。总之,这些证明了元蛋白质组学在重要肠道细菌物种表征中的应用。研究人类肠道微生物组的许多参考基因组是可用的,但关于微生物如何工作的知识是有限的。在单个物种或群落水平上鉴定蛋白质可以直接了解微生物的功能。通过分析1000多个元蛋白质组学数据集,我们研究了2000多个微生物物种的蛋白质景观,这些微生物物种可能对人类健康和疾病很重要。这项工作展示了元蛋白组学数据集在研究个体基因组方面的新应用。我们通过一个名为GutBac的网站提供了分析结果,我们相信该网站将成为研究对人类健康和疾病重要的微生物物种的资源。
Host-microbiome interactions and the microbial community have broad impact in human health and diseases. Most microbiome based studies are performed at the genome level based on next-generation sequencing techniques, but metaproteomics is emerging as a powerful technique to study microbiome functional activity by characterizing the complex and dynamic composition of microbial proteins. We conducted a large-scale survey of human gut microbiome metaproteomic data to identify generalist species that are ubiquitously expressed across all samples and specialists that are highly expressed in a small subset of samples associated with a certain phenotype. We were able to utilize the metaproteomic mass spectrometry data to reveal the protein landscapes of these species, which enables the characterization of the expression levels of proteins of different functions and underlying regulatory mechanisms, such as operons. Finally, we were able to recover a large number of open reading frames (ORFs) with spectral support, which were missed by de novo protein-coding gene predictors. We showed that a majority of the rescued ORFs overlapped with de novo predicted protein-coding genes, but on opposite strands or in different frames. Together, these demonstrate applications of metaproteomics for the characterization of important gut bacterial species. Many reference genomes for studying human gut microbiome are available, but knowledge about how microbial organisms work is limited. Identification of proteins at individual species or community level provides direct insight into the functionality of microbial organisms. By analyzing more than a thousand metaproteomics datasets, we examined protein landscapes of more than two thousands of microbial species that may be important to human health and diseases. This work demonstrated new applications of metaproteomic datasets for studying individual genomes. We made the analysis results available through a website (called GutBac), which we believe will become a resource for studying microbial species important for human health and diseases.
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